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Therapy Insight: preserving fertility in cyclophosphamide-treated patients with rheumatic disease

Nature Clinical Practice Rheumatology volume 4, pages 250–257 (2008)Cite this article

Abstract

Cyclophosphamide remains a necessary treatment for severe rheumatic diseases, despite the continued search for alternative therapies with less gonadal toxicity. The risk of premature gonadal failure and sterility might lead young patients to delay treatment with cyclophosphamide. The patient's age at treatment and the cumulative dose received remain important risk factors for cyclophosphamide-induced gonadal failure in both males and females. Estrogen-containing oral contraceptives for females and testosterone for males are suggested to reduce the gonadal toxicity of cyclophosphamide, although few studies support these interventions. Owing to increased side effects, hormonal therapy is often avoided in patients with edema, hypertension, nephrotic syndrome or antiphospholipid antibodies. Agonists and antagonists of gonadotropin receptors are under study. Gonadotropin-receptor agonists might have beneficial effects in addition to suppression of sex-hormone production. The outcome of attempted cryopreservation of eggs, embryos or ovaries remains uncertain for women seeking to preserve their reproductive potential. Storing male gametes before chemotherapy is widely practiced and technically successful. As recovery of menses or production of testosterone does not predict individual fertility, identification of biomarkers of gonadal function and reserve, including serum levels of several hormones, ultrasonographic measurements of ovarian volume and antral follicle count, are necessary.

Key Points

  • Cyclophosphamide-induced gonadal toxicity remains a significant problem in patients with severe rheumatic disease

  • Receiving cyclophosphamide treatment before the onset of puberty does not reduce gonadal toxicity, especially in males

  • Sperm storage remains the most viable option for postpubertal males to preserve their reproductive options

  • Women should consider treatment with gonadotropin-releasing-hormone agonists in advance of cyclophosphamide therapy to decrease the risk of gonadal toxicity

  • Cryopreservation of embryos is feasible but presents substantial obstacles, including the need for ovarian stimulation and fertilization, which are difficult to achieve during an acute episode of systemic lupus erythematosus nephritis

  • Techniques such as oocyte cryopreservation or ovarian-tissue cryopreservation remain experimental, but might be future options for preserving reproductive potential, particularly in prepubertal girls

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Figure 1: The menstrual cycle.
Figure 2: Procedures for assisted reproduction (male infertility).

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Authors and Affiliations

  1. MA Dooley is Director of the University of North Carolina Rheumatology Clinic, Chapel Hill, NC, USA, and Associate Professor of Medicine at the University of North Carolina at Chapel Hill, where R Nair is a Rheumatology Fellow.,

    Mary Anne Dooley & Raj Nair

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  1. Mary Anne Dooley
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Correspondence to Mary Anne Dooley.

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Dooley, M., Nair, R. Therapy Insight: preserving fertility in cyclophosphamide-treated patients with rheumatic disease. Nat Rev Rheumatol 4, 250–257 (2008). https://doi.org/10.1038/ncprheum0770

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